<p>Alpha-1 Antitrypsin Induces Epithelial-to-Mesenchymal Transition, Endothelial-to-Mesenchymal Transition, and Drug Resistance in Lung Cancer Cells</p>

Abstract

Alpha-1 antitrypsin (A1AT) is a secreted protein that plays an important role in various diseases. However, the role of A1AT in non-small cell lung cancer is obscure. Materials and Methods: A1AT expression in non-small cell lung cancer was analyzed using quantitative reverse transcription PCR, Western blotting (WB), immunohistochemistry (IHC), and ELISA. WB and IF were used to analyze markers of epithelial-to-mesenchymal transition (EMT), EndoMT, and cancer stem cell (CSC). Transwell and cell wound healing assays were used to analyze migration and invasion abilities. Colony formation and CCK-8 assays were used to analyze cell proliferation following cisplatin treatment. Results: A1AT expression was higher in lung cancer samples than in normal tissues and the increased expression was correlated with poor overall survival of patients. In vitro experiments showed that A1AT overexpressed by plasmid transfection significantly promoted migration, invasion, EMT, EndoMT, stemness, and colony formation in lung cancer cell lines, as opposed to A1AT downregulation by siRNA transfection, which significantly inhibited all these variables. Conclusion: A1AT is a novel therapeutic target and might be associated with tumor metastasis in lung carcinoma.

<p>LncRNA LINC01116 Contributes to Cisplatin Resistance in Lung Adenocarcinoma</p>

“…Previous studies have extensively investigated the mechanisms responsible for resistance to cisplatin in NSCLC. Alpha-1 antitrypsin (A1AT), a member of the serpin (serine protease inhibitor) family, was recently reported to induce cisplatin resistance in NSCLC, 36 and large tumour suppressor (LATS) kinases were found to contribute to cisplatin resistance in advanced NSCLC. 37 FAM83D, an oncoprotein in multiple human cancer, was identified to promote cisplatin resistance in NSCLC via the AKT/mTOR pathway, 38 and CLEC4M, a Ca 2+ -dependent C-type lectin, was reported to promote cisplatin resistance in NSCLC.…”

Alpha-1 antitrypsin deficiency and risk of lung cancer in never-smokers: a multicentre case–control study

“…It displays characteristics that distinguish it from LC in smokers, including a number of genes [ 6 ] and their protein products, which could act at different levels in the process of carcinogenesis and tumour progression. Among these is alpha-1 antitrypsin (AAT) [ 7 , 8 ], which is a glycoprotein synthesized primarily by hepatocytes (80%) and, to a lesser extent, by other cells such as monocytes, macrophages or neoplastic cells among others [ 9 ]. It is encoded by the SERPINA1 gene, located in the long arm of chromosome 14 [ 10 ], and is transmitted by autosomal co-dominant Mendelian inheritance [ 11 ].…”

“…The principal action of AAT is inhibition of serine protease, with neutrophil elastase being the most important at a tissular level [ 15 ]. Other properties described are anti-inflammatory, antimicrobial and immunomodulatory activity [ 16 , 17 ], which has led to establish the possible involvement of AAT in the development and progression of different types of neoplasms [ 18 ], including LC [ 7 , 19 ]. The organ most commonly affected by AATD in adults is the lung, through the development of emphysema, especially among individuals with exposure to tobacco smoke [ 20 ].…”

Alpha-1 Antitrypsin Deficiency and Risk of Lung Cancer in Never-Smokers: A Multicentre Case-Control Study

“…It displays characteristics that distinguish it from LC in smokers, including a number of genes (6) and their protein products, which could act at different levels in the process of carcinogenesis and tumour progression. Among these is alpha-1 antitrypsin (AAT) (7,8), which is a glycoprotein synthesized primarily by hepatocytes (80%) and, to a lesser extent, by other cells such as monocytes, macrophages or neoplastic cells among others (9). It is encoded by the SERPINA1 gene, located in the long arm of chromosome 14 (10), and is transmitted by autosomal co-dominant Mendelian inheritance (11).…”

“…The principal action of AAT is inhibition of serine protease, with neutrophil elastase being the most important at a tissular level (15). Other properties described are anti-in ammatory, antimicrobial and immunomodulatory activity (16,17), which has led to establish the possible involvement of AAT in the development and progression of different types of neoplasms (18), including LC (7,19). The organ most commonly affected by AATD in adults is the lung, through the development of emphysema, especially among individuals with exposure to tobacco smoke (20).…”